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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 牟中原(Chung-Yuan Mou) | |
| dc.contributor.author | Yu-Hsuan Lin | en |
| dc.contributor.author | 林郁萱 | zh_TW |
| dc.date.accessioned | 2021-06-16T06:34:35Z | - |
| dc.date.available | 2019-08-08 | |
| dc.date.copyright | 2014-08-08 | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2014-08-04 | |
| dc.identifier.citation | 1. Tsuneo Yanagisawa, T.S., Kazuyuki Kuroda, Chuzo Kato The Preparation of Alkyltriinethylaininonium–Kaneinite Complexes and Their Conversion to Microporous Materials. Bull. Chem. Soc. Jpn 63, 988-992 (1990).
2. C. T. Kresge, M.E.L., W. J. Roth, J. C. vartuli, J. S. Beck Ordered mesoporous molecular sieves synthesized by a liquid crystal template mechanism. Nature 359, 710-712 (1992). 3. Hoffmann, F., Cornelius, M., Morell, J. & Froba, M. Silica-Based Mesoporous Organic–Inorganic Hybrid Materials. Angewandte Chemie International Edition 45, 3216-3251 (2006). 4. Tang, F., Li, L. & Chen, D. Mesoporous Silica Nanoparticles: Synthesis, Biocompatibility and Drug Delivery. Advanced Materials 24, 1504-1534 (2012). 5. Kwon, S. et al. Silica-based mesoporous nanoparticles for controlled drug delivery. Journal of Tissue Engineering 4 (2013). 6. Wu, S.-H., Mou, C.-Y. & Lin, H.-P. Synthesis of mesoporous silica nanoparticles. Chemical Society Reviews 42, 3862-3875 (2013). 7. Taguchi, A. & Schuth, F. Ordered mesoporous materials in catalysis. Microporous and Mesoporous Materials 77, 1-45 (2005). 8. Heitbaum, M., Glorius, F. & Escher, I. Asymmetric heterogeneous catalysis. Angewandte Chemie (International ed. in English) 45, 4732-4762 (2006). 9. Chew, T.L., Ahmad, A.L. & Bhatia, S. Ordered mesoporous silica (OMS) as an adsorbent and membrane for separation of carbon dioxide (CO2). Advances in colloid and interface science 153, 43-57 (2010). 10. Belmabkhout, Y. & Sayari, A. Effect of pore expansion and amine functionalization of mesoporous silica on CO2 adsorption over a wide range of conditions. Adsorption 15, 318-328 (2009). 11. Wu, S.H., Hung, Y. & Mou, C.Y. Mesoporous silica nanoparticles as nanocarriers. Chem Commun (Camb) 47, 9972-9985 (2011). 12. Lin, Y.-S., Hurley, K.R. & Haynes, C.L. Critical Considerations in the Biomedical Use of Mesoporous Silica Nanoparticles. The Journal of Physical Chemistry Letters 3, 364-374 (2012). 13. Lev, O. et al. Organically modified sol-gel sensors. Analytical Chemistry 67, 22A-30A (1995). 14. Aelion, R., Loebel, A. & Eirich, F. Hydrolysis of Ethyl Silicate*. Journal of the American Chemical Society 72, 5705-5712 (1950). 15. Lin, H.-P. & Mou, C.-Y. Structural and Morphological Control of Cationic Surfactant-Templated Mesoporous Silica. Accounts of Chemical Research 35, 927-935 (2002). 16. Werner Stober, A.F. Controlled growth of monodisperse silica spheres in the micron size range. Journal of Colloid and Interface Science 26, 62-69 (1968). 17. Grun, M., Lauer, I. & Unger, K.K. The synthesis of micrometer- and submicrometer-size spheres of ordered mesoporous oxide MCM-41. Advanced Materials 9, 254-257 (1997). 18. Nooney, R.I., Thirunavukkarasu, D., Chen, Y., Josephs, R. & Ostafin, A.E. Synthesis of Nanoscale Mesoporous Silica Spheres with Controlled Particle Size. Chemistry of Materials 14, 4721-4728 (2002). 19. Chiang, Y.-D. et al. Controlling Particle Size and Structural Properties of Mesoporous Silica Nanoparticles Using the Taguchi Method. The Journal of Physical Chemistry C 115, 13158-13165 (2011). 20. Lin, Y.-S. et al. Well-Ordered Mesoporous Silica Nanoparticles as Cell Markers. Chemistry of Materials 17, 4570-4573 (2005). 21. Lu, F., Wu, S.-H., Hung, Y. & Mou, C.-Y. Size Effect on Cell Uptake in Well-Suspended, Uniform Mesoporous Silica Nanoparticles. Small 5, 1408-1413 (2009). 22. Vivero-Escoto, J.L., Huxford-Phillips, R.C. & Lin, W. Silica-based nanoprobes for biomedical imaging and theranostic applications. Chemical Society Reviews 41, 2673-2685 (2012). 23. Asefa, T. & Tao, Z. Biocompatibility of Mesoporous Silica Nanoparticles. Chemical Research in Toxicology 25, 2265-2284 (2012). 24. M. Vallet-Regi, A.R.m., R. P. del Real, and J. Pe’rez-Pariente A New Property of MCM-41 Drug Delivery System. Chemistry of materials 13, 308-311 (2001). 25. Lai, C.-Y. et al. A Mesoporous Silica Nanosphere-Based Carrier System with Chemically Removable CdS Nanoparticle Caps for Stimuli-Responsive Controlled Release of Neurotransmitters and Drug Molecules. Journal of the American Chemical Society 125, 4451-4459 (2003). 26. Singh, N. et al. Bioresponsive Mesoporous Silica Nanoparticles for Triggered Drug Release. Journal of the American Chemical Society 133, 19582-19585 (2011). 27. Lin, Q. et al. Anticancer Drug Release from a Mesoporous Silica Based Nanophotocage Regulated by Either a One- or Two-Photon Process. Journal of the American Chemical Society 132, 10645-10647 (2010). 28. Lee, C.-H. et al. Intracellular pH-Responsive Mesoporous Silica Nanoparticles for the Controlled Release of Anticancer Chemotherapeutics. Angewandte Chemie International Edition 49, 8214-8219 (2010). 29. Liong, M. et al. Multifunctional Inorganic Nanoparticles for Imaging, Targeting, and Drug Delivery. ACS Nano 2, 889-896 (2008). 30. Radu, D.R. et al. A Polyamidoamine Dendrimer-Capped Mesoporous Silica Nanosphere-Based Gene Transfection Reagent. Journal of the American Chemical Society 126, 13216-13217 (2004). 31. Ashley, C.E. et al. Delivery of Small Interfering RNA by Peptide-Targeted Mesoporous Silica Nanoparticle-Supported Lipid Bilayers. ACS Nano 6, 2174-2188 (2012). 32. Chen, Y.-P. et al. A New Strategy for Intracellular Delivery of Enzyme Using Mesoporous Silica Nanoparticles: Superoxide Dismutase. Journal of the American Chemical Society 135, 1516-1523 (2013). 33. Rosenholm, J.M., Peuhu, E., Eriksson, J.E., Sahlgren, C. & Linden, M. Targeted Intracellular Delivery of Hydrophobic Agents using Mesoporous Hybrid Silica Nanoparticles as Carrier Systems. Nano Letters 9, 3308-3311 (2009). 34. Colilla, M., Gonzalez, B. & Vallet-Regi, M. Mesoporous silica nanoparticles for the design of smart delivery nanodevices. Biomaterials Science 1, 114-134 (2013). 35. Williams, D.F. On the mechanisms of biocompatibility. Biomaterials 29, 2941-2953 (2008). 36. Halas, N.J. Nanoscience under Glass: The Versatile Chemistry of Silica Nanostructures. ACS Nano 2, 179-183 (2008). 37. Garcia-Bennett, A.E. Synthesis, toxicology and potential of ordered mesoporous materials in nanomedicine. Nanomedicine 6, 867-877 (2011). 38. Hudson, S.P., Padera, R.F., Langer, R. & Kohane, D.S. The biocompatibility of mesoporous silicates. Biomaterials 29, 4045-4055 (2008). 39. He, Q., Zhang, Z., Gao, F., Li, Y. & Shi, J. In vivo Biodistribution and Urinary Excretion of Mesoporous Silica Nanoparticles: Effects of Particle Size and PEGylation. Small 7, 271-280 (2011). 40. Veronese, F.M. & Pasut, G. PEGylation, successful approach to drug delivery. Drug Discovery Today 10, 1451-1458 (2005). 41. Ishida, T. et al. Injection of PEGylated liposomes in rats elicits PEG-specific IgM, which is responsible for rapid elimination of a second dose of PEGylated liposomes. Journal of Controlled Release 112, 15-25 (2006). 42. Geng, Y. et al. Shape effects of filaments versus spherical particles in flow and drug delivery. Nat Nano 2, 249-255 (2007). 43. Meng, H. et al. Aspect Ratio Determines the Quantity of Mesoporous Silica Nanoparticle Uptake by a Small GTPase-Dependent Macropinocytosis Mechanism. ACS Nano 5, 4434-4447 (2011). 44. Nel, A., Xia, T., Madler, L. & Li, N. Toxic Potential of Materials at the Nanolevel. Science 311, 622-627 (2006). 45. Lin, Y.-S. & Haynes, C.L. Impacts of Mesoporous Silica Nanoparticle Size, Pore Ordering, and Pore Integrity on Hemolytic Activity. Journal of the American Chemical Society 132, 4834-4842 (2010). 46. Piao, Y., Burns, A., Kim, J., Wiesner, U. & Hyeon, T. Designed Fabrication of Silica-Based Nanostructured Particle Systems for Nanomedicine Applications. Advanced Functional Materials 18, 3745-3758 (2008). 47. Slowing, I., Trewyn, B.G. & Lin, V.S.Y. Effect of Surface Functionalization of MCM-41-Type Mesoporous Silica Nanoparticles on the Endocytosis by Human Cancer Cells. Journal of the American Chemical Society 128, 14792-14793 (2006). 48. Chung, E.J. et al. Transduction of PTEN Proteins Using the Tat Domain Modulates TGF-β1–Mediated Signaling Pathways and Transdifferentiation in Subconjunctival Fibroblasts. Investigative Ophthalmology & Visual Science 53, 379-386 (2012). 49. Bornscheuer, U.T. Immobilizing Enzymes: How to Create More Suitable Biocatalysts. Angewandte Chemie International Edition 42, 3336-3337 (2003). 50. Futaki, S. et al. Arginine-rich Peptides: AN ABUNDANT SOURCE OF MEMBRANE-PERMEABLE PEPTIDES HAVING POTENTIAL AS CARRIERS FOR INTRACELLULAR PROTEIN DELIVERY. Journal of Biological Chemistry 276, 5836-5840 (2001). 51. Richard, J.P. et al. Cell-penetrating Peptides: A REEVALUATION OF THE MECHANISM OF CELLULAR UPTAKE. Journal of Biological Chemistry 278, 585-590 (2003). 52. Nagahara, H. et al. Transduction of full-length TAT fusion proteins into mammalian cells: TAT-p27(Kip1) induces cell migration. Nature Medicine 4, 1449-1452 (1998). 53. Winterbourn, C.C. & Hampton, M.B. Thiol chemistry and specificity in redox signaling. Free Radical Biology and Medicine 45, 549-561 (2008). 54. Brieger, K., Schiavone, S., Miller, F.J., Jr. & Krause, K.H. Reactive oxygen species: from health to disease. Swiss medical weekly 142, w13659 (2012). 55. Mandal, D.A. The News-Medical.net; 2012). 56. Diehn, M. et al. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 458, 780-783 (2009). 57. Okamoto, K. et al. Formation of 8-hydroxy-2′-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins in human renal-cell carcinoma. International Journal of Cancer 58, 825-829 (1994). 58. Pryor, W.A. & Stone, K. Oxidants in Cigarette Smoke Radicals, Hydrogen Peroxide, Peroxynitrate, and Peroxynitritea. Annals of the New York Academy of Sciences 686, 12-27 (1993). 59. Paravicini, T.M. & Touyz, R.M. NADPH Oxidases, Reactive Oxygen Species, and Hypertension: Clinical implications and therapeutic possibilities. Diabetes Care 31, S170-S180 (2008). 60. Block, M.L., Zecca, L. & Hong, J.-S. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8, 57-69 (2007). 61. Halliwell, B. in Free Radicals in the Brain. (eds. L. Packer, L. Prilipko & Y. Christen) 21-40 (Springer Berlin Heidelberg, 1992). 62. Multhaup, G. et al. Reactive oxygen species and Alzheimer's disease. Biochemical Pharmacology 54, 533-539 (1997). 63. Banfi, B. et al. NOX3, a Superoxide-generating NADPH Oxidase of the Inner Ear. Journal of Biological Chemistry 279, 46065-46072 (2004). 64. Koli, K., Myllarniemi, M., Keski-Oja, J. & Kinnula, V.L. Transforming growth factor-beta activation in the lung: focus on fibrosis and reactive oxygen species. Antioxidants & redox signaling 10, 333-342 (2008). 65. Snelgrove, R.J., Edwards, L., Rae, A.J. & Hussell, T. An absence of reactive oxygen species improves the resolution of lung influenza infection. European Journal of Immunology 36, 1364-1373 (2006). 66. Korenaga, M. et al. Hepatitis C Virus Core Protein Inhibits Mitochondrial Electron Transport and Increases Reactive Oxygen Species (ROS) Production. Journal of Biological Chemistry 280, 37481-37488 (2005). 67. Glucose Challenge Stimulates Reactive Oxygen Species (ROS) Generation by Leucocytes. The Journal of Clinical Endocrinology & Metabolism 85, 2970-2973 (2000). 68. Cooke, M.S., Mistry, N., Wood, C., Herbert, K.E. & Lunec, J. Immunogenicity of DNA Damaged by Reactive Oxygen Species—Implications for Anti-DNA Antibodies in Lupus. Free Radical Biology and Medicine 22, 151-159 (1997). 69. Stanner, S., Hughes, J., Kelly, C. & Buttriss, J. A review of the epidemiological evidence for the ‘antioxidant hypothesis’. Public Health Nutrition 7, 407-422 (2004). 70. Mursu, J., Robien, K., Harnack, L.J., Park, K. & Jacobs, D.R. Dietary supplements and mortality rate in older women: The iowa women's health study. Archives of Internal Medicine 171, 1625-1633 (2011). 71. McCord, J.M. & Fridovich, I. Superoxide Dismutase: AN ENZYMIC FUNCTION FOR ERYTHROCUPREIN (HEMOCUPREIN). Journal of Biological Chemistry 244, 6049-6055 (1969). 72. Paglia, D.E. & Valentine, W.N. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70, 158-169 (1967). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57085 | - |
| dc.description.abstract | 中孔洞氧化矽奈米粒子由於具有高表面積、單一孔洞大小以及容易進行官能基修飾等特性，使其常作為多功能型的奈米材料。在生物應用方面，因為中孔洞氧化矽奈米粒子具有極好的生物相容性及可分解性，因此被廣泛地運用在奈米生醫方面的研究，例如控制藥物進行定點釋放、蛋白質及基因的載體、醫學造影以及生物偵測等。
活性氧化物質 (ROS) 在生物體內扮演重要的角色，除了抵禦外來有機體及幫助細胞間訊號傳遞外，過去也有許多研究顯示ROS和許多疾病 (癌症、高血壓、糖尿病等) 的形成習習相關。在人體內，有許多抗氧化物質能夠精準地控制ROS含量，其中，過氧化物歧化酶 (SOD) 以及谷胱甘肽過氧化物酶 (GPx) 是主要的兩種蛋白質。過氧化物歧化酶將超氧陰離子 (O2•-) 還原成過氧化氫；谷胱甘肽過氧化物酶再將過氧化氫分解成水。 這篇論文中，我們設計出具有催化功能的中孔洞氧化矽奈米粒子，其可有效地減少ROS並進一步的降低細胞內的氧化壓力。此奈米粒子可分為三個部分，分別是中孔洞二氧化矽奈米粒子、連接鏈以及抗氧化蛋白。首先，先利用共縮合及後修飾的方式將螢光分子FITC和NTA-Ni 修飾在中孔洞氧二化矽奈米粒子上。接著，利用基因工程的方式使TAT分別和SOD及GPx形成融合蛋白 (fusion protein)。最後，利用鎳及His-tag所形成的配位共價鍵來連接奈米粒子及抗氧化蛋白。我們利用人類免疫缺陷病毒中的反活化轉錄因子蛋白 (TAT) 能高效率穿越細胞膜的特性，希望能將奈米粒子更有效的送進細胞內。 在這研究的最後，我們將兩種帶有不同蛋白的奈米粒子 (FMSN-TAT-SOD、FMSN-TAT-GPx) 共同送進細胞內，最後我們找到了降低細胞內ROS效率最好的蛋白比例。在這個比例之下，我們可以有效的提升受到氧化壓力刺激的細胞存活率。我們預期這結果能使中孔洞二氧化矽奈米粒子在蛋白質治療上有更進一步的運用。 | zh_TW |
| dc.description.abstract | Mesoporous silica nanoparticle (MSN) was used as a multifunctional material because of its characteristics, such as high surface area, uniform pore size and easy functionalization. Besides, MSN is very suitable for biological applications such as controlled drug release, cell labeling and enzyme delivery due to the properties of biocompatibility and degradability.
As well known, ROS played a crucial role in many diseases and was defensed by superoxide dismutase (SOD) and glutathione peroxidase (GPx) which are two major antioxidant enzymes in physiological condition. The SOD scavenges superoxide radicals into hydrogen peroxide and GPx can convert hydrogen peroxide into water. In this study, we designed a catalytic MSN as a nanoreactor for scavenging ROS to reduce oxidative damages. The nanoreactor consists of three parts; namely, MSN, tether and enzymes. MSN was first synthesized with FITC and then modified by conjugating silane tether (NTA-Ni) to form FMSN-NTA-Ni. The fusion proteins of His-tagged TAT-hSOD and His-tagged TAT-hGPx were constructed and expressed by using genetic engineering method. Finally, the two fusion proteins are conjugated on the MSN surface respectively through the nickel and His-tagged interaction to compose sequential ROS scavengers. HIV transactivator protein (TAT) containing MSN was considered as an effective method in order to increasing the transmembrane permeability of nanoparticles. We finally demonstrated a two different functionalized-MSNs co-delivery into cells which can decline ROS efficiently. This study becomes a novel and promising tool for future therapeutic approach. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T06:34:35Z (GMT). No. of bitstreams: 1 ntu-103-R01223207-1.pdf: 2525627 bytes, checksum: d5208681a06dff4966f043a3e066a996 (MD5) Previous issue date: 2014 | en |
| dc.description.tableofcontents | 口試委員會審定書 #
謝誌 i 中文摘要 iii ABSTRACT iv CONTENTS v LIST OF FIGURES viii LIST OF TABLES xii Chapter 1 Introduction 1 1.1 Ordered Mesoporous Silica 1 1.2 Synthesis of Mesoporous Silica Nanoparticles 3 1.2.1 Silica Sol-Gel Chemistry 3 1.2.2 Modified Stober Methods 5 1.2.3 Mechanism 7 1.2.4 Functionalization of MSNs 8 1.3 Biological Application of MSNs 11 1.3.1 MSNs-Based Drug Delivery 15 1.3.2 Protein Delivery 16 1.4 Reactive Oxygen Species (ROS) and Diseases 17 1.5 Motivation 20 Chapter 2 Materials and Methods 21 2.1 Synthesis of Fluorescent Mesoporous Silica Nanoparticles 21 2.2 Synthetic Scheme for NTA-Silane Linker 21 2.3 Conjugation of NTA-silane and Ni (II) with FMSN 22 2.4 Immobilization of His-TAT-Protein with FMSN-NTA-Ni 22 2.5 Characterization 23 2.6 Cell Liens and Reagents 23 2.7 Plasmid Construction 24 2.7.1 Human Cu, Zn-SOD 24 2.7.2 Human glutathione peroxidase 1 Sec49C mutant 25 2.8 Expression and Purification of Recombinant Proteins 26 2.9 Cell Culture 26 2.10 Western Blotting Analysis 27 2.11 Determination of Superoxide Dismutase and Glutathione Peroxidase Activity 27 2.12 Cell Viability Assay 28 2.13 Flow Cytometry Analysis 29 2.14 Immunocytochemical Staining for Proteins Expression 29 Chapter 3 Results and Discussion 30 3.1 Characterization of Fluorescence Mesoporous Silica Nanoparticles 31 3.2 Delivery of FMSN-TAT-Proteins into HeLa cell 35 3.2.1 Cytotoxicity of Nanoparticles 35 3.2.2 Delivery efficiency and distribution pattern of Nanoparticles 36 3.2.3 Refolded Enzymes Activity Assay 41 3.2.4 FMSN-TAT-Proteins Decrease Superoxide Anion Stress 44 3.2.5 Sequential Reactions in Co-delivery of FMSN-TAT-SOD and FMSN-TAT-GPx 46 Chapter 4 Conclusions 49 Chapter 5 References 50 | |
| dc.language.iso | en | |
| dc.subject | 活性氧化物質 | zh_TW |
| dc.subject | 抗氧化蛋白 | zh_TW |
| dc.subject | 中孔洞矽奈米粒子 | zh_TW |
| dc.subject | antioxidant | en |
| dc.subject | mesoporous silica nanoparticle | en |
| dc.subject | ROS | en |
| dc.title | 奈米粒子負載及輸送超氧化物歧化酶及谷胱甘肽過氧化物酶 | zh_TW |
| dc.title | Characterization on co-delivery of Superoxide Dismutase and Glutathione Peroxidase by Using Nanoparticles | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 102-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳建志(Chien-Tsu Chen),簡汎清(Fan-Ching Chien) | |
| dc.subject.keyword | 中孔洞矽奈米粒子,抗氧化蛋白,活性氧化物質, | zh_TW |
| dc.subject.keyword | mesoporous silica nanoparticle,antioxidant,ROS, | en |
| dc.relation.page | 57 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2014-08-04 | |
| dc.contributor.author-college | 理學院 | zh_TW |
| dc.contributor.author-dept | 化學研究所 | zh_TW |
| 顯示於系所單位： | 化學系 | |
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